Abstract

This study reviewed the evidence that assessed the association between maternal pre-pregnancy body mass index (BMI) and/or gestational weight gain and offspring body composition in childhood. A systematic review was conducted. Cohort studies, case-control studies and randomized controlled trials measuring offspring body composition by indirect methods were included. Meta-analyses of the effect of pre-pregnancy BMI on offspring fat-free mass, body fat percent, and fat mass were conducted through random-effects models. 20 studies were included, most of which reported a positive association of pre-pregnancy BMI with offspring body fat. Standardized mean differences in body fat percent, fat mass and fat-free mass between infants of women with normal pre-pregnancy BMI and those of overweight/obese women were 0.31 percent points (95%CI: 0.19; 0.42), 0.38kg (95%CI: 0.26; 0.50), and 0.18kg (95%CI: -0.07; 0.42), respectively. Evidence so far suggests that pre-pregnancy maternal overweight is associated with higher offspring adiposity.

Obesity; Pregnancy; Body Composition; Adiposity

Resumen

Esta revisión evaluó la asociación entre el índice de masa corporal (IMC) pregestacional y/o el aumento de peso gestacional con la composición corporal de los hijos en la infancia. Se realizó una revisión sistemática. Se incluyeron estudios de cohorte, caso-control y ensayos randomizados, que determinaron la composición corporal de los hijos mediante métodos indirectos. Se realizaron metaanálisis del efecto del IMC pregestacional sobre la masa libre de grasa, porcentaje de grasa corporal y masa de grasa. Se incluyeron 18 estudios, la mayoría de los cuales reportó asociación positiva entre el IMC materno pregestacional y la adiposidad de los hijos. Las diferencias de medias padronizadas de porcentaje de grasa corporal, masa de grasa y masa libre de grasa entre hijos de mujeres con IMC pregestacional normal, en comparación con los de mujeres con sobrepeso/obesidad fueron: 0,31 puntos porcentuales (IC95%: 0,19; 0,42), 0,38kg (IC95%: 0,26; 0,50) y 0,18kg (IC95%: -0,07; 0,42), respectivamente. Esta evidencia sugiere que el sobrepeso materno pregestacional se asocia con una elevada adiposidad en sus hijos.

Obesidad; Embarazo; Composición Corporal; Adiposidad

Resumo

Esta revisão avaliou a associação entre o índice de massa corporal (IMC) pré-gestacional e/ou ganho de peso gestacional com a composição corporal dos filhos na infância. Uma revisão sistemática foi realizada. Estudos de coorte, caso-controle e ensaios randomizados, que determinaram a composição corporal dos filhos mediante métodos indiretos, foram incluídos. Meta-análises do efeito do IMC pré-gestacional sobre a massa livre de gordura, percentual de gordura corporal e massa gorda foram realizados. Incluiu-se 18 estudos, a maioria dos quais reportou associação positiva entre o IMC materno pré-gestacional e adiposidade dos filhos. As diferenças de médias padronizadas de percentual de gordura corporal, massa gorda e massa livre de gordura entre filhos de mulheres com IMC pré-gestacional normal em comparação com os de mulheres com sobrepeso/obesidade foram: 0,31 pontos percentuais (IC95%: 0,19; 0,42), 0,38kg (IC95%: 0,26; 0,50) e 0,18kg (IC95%: -0,07; 0,42), respectivamente. Esta evidência sugere que o sobrepeso materno pré-gestacional está associado com a elevada adiposidade em seus filhos.

Obesidade; Gravidez; Composição Corporal; Adiposidade

Introduction

According to observational studies, carried out in high income countries, maternal lifestyle, dietary habits, physical activity and work hours could influence offspring size at birth, and weight development in childhood ¹1. Symonds ME, Mendez MA, Meltzer HM, Koletzko B, Godfrey K, Forsyth S, et al. Early life nutritional programming of obesity: mother-child cohort studies. Ann Nutr Metab 2013; 62:137-45.,²2. Kramer MS. Determinants of low birth weight: methodological assessment and meta-analysis. Ann Nutr Metab 1987; 65:663-737.,³3. Schlussel MM, Souza EB, Reichenheim ME, Kac G. Physical activity during pregnancy and maternal-child health outcomes: a systematic literature review. Cad Saúde Pública 2008; 24 Suppl 4:531-44.. Pre-pregnancy and gestational maternal body composition may impact offspring body fat mass at birth, in childhood and in adolescence, and may also predict the risk of obesity in adulthood ⁴4. Armitage JA, Poston L, Taylor PD. Developmental origins of obesity and the metabolic syndrome: the role of maternal obesity. Front Horm Res 2008; 36:73-84.,⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,⁷7. Laitinen J, Power C, Jarvelin MR. Family social class, maternal body mass index, childhood body mass index, and age at menarche as predictors of adult obesity. Am J Clin Nutr 2001; 74:287-94.,⁸8. Tequeanes AL, Gigante DP, Assuncao MC, Chica DA, Horta BL. Maternal anthropometry is associated with the body mass index and waist:height ratio of offspring at 23 years of age. J Nutr 2009; 139:750-4.. The increase in the prevalence of maternal obesity in recent decades ⁹9. Ehrenberg HM, Dierker L, Milluzzi C, Mercer BM. Prevalence of maternal obesity in an urban center. Am J Obstet Gynecol 2002; 187:1189-93.,¹⁰10. Lu GC, Rouse DJ, DuBard M, Cliver S, Kimberlin D, Hauth JC. The effect of the increasing prevalence of maternal obesity on perinatal morbidity. Am J Obstet Gynecol 2001; 185:845-9.has occurred in parallel with the increment of large for gestational age newborns¹¹11. Ehrenberg HM, Mercer BM, Catalano PM. The influence of obesity and diabetes on the prevalence of macrosomia. Am J Obstet Gynecol 2004; 191:964-8.,¹²12. Jensen DM, Damm P, Sorensen B, Molsted-Pedersen L, Westergaard JG, Ovesen P, et al. Pregnancy outcome and prepregnancy body mass index in 2459 glucose-tolerant Danish women. Am J Obstet Gynecol 2003; 189:239-44.,¹³13. Surkan PJ, Hsieh CC, Johansson AL, Dickman PW, Cnattingius S. Reasons for increasing trends in large for gestational age births. Obstet Gynecol 2004; 104:720-6.and an increased incidence of childhood obesity ¹⁴14. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006; 295:1549-55.. Female offspring of obese women are most likely to be obese predisposing their children to obesity, insulin resistance and diabetes⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,¹⁵15. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005; 115:290-6.,¹⁶16. Pettitt DJ, Baird HR, Aleck KA, Bennett PH, Knowler WC. Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy. N Engl J Med 1983; 308:242-5.. Several studies have shown that a high increment in maternal gestational weight gain associated with increased offspring body mass index (BMI) ¹⁷17. Mamun AA, O'Callaghan M, Callaway L, Williams G, Najman J, Lawlor DA. Associations of gestational weight gain with offspring body mass index and blood pressure at 21 years of age: evidence from a birth cohort study. Circulation 2009; 119:1720-7.,¹⁸18. Moreira P, Padez C, Mourão-Carvalhal I, Rosado V. Maternal weight gain during pregnancy and overweight in Portuguese children. Int J Obes (Lond) 2007; 31:608-14.,¹⁹19. Oken E, Taveras EM, Kleinman KP, Rich-Edwards JW, Gillman MW. Gestational weight gain and child adiposity at age 3 years. Am J Obstet Gynecol 2007; 196:322.e1-8. whereas other studies have reported no such association ²⁰20. Catalano PM, Drago NM, Amini SB. Maternal carbohydrate metabolism and its relationship to fetal growth and body composition. Am J Obstet Gynecol 1995; 172:1464-70.,²¹21. Koupil I, Toivanen P. Social and early-life determinants of overweight and obesity in 18-year-old Swedish men. Int J Obes (Lond) 2008; 32:73-81.. In consequence, across a number of generations a potential intergenerational cycle of increased risk of obesity and metabolic sequelae in the offspring of obese mothers is expected, with important implications for public health policies ⁴4. Armitage JA, Poston L, Taylor PD. Developmental origins of obesity and the metabolic syndrome: the role of maternal obesity. Front Horm Res 2008; 36:73-84.,¹¹11. Ehrenberg HM, Mercer BM, Catalano PM. The influence of obesity and diabetes on the prevalence of macrosomia. Am J Obstet Gynecol 2004; 191:964-8.,¹²12. Jensen DM, Damm P, Sorensen B, Molsted-Pedersen L, Westergaard JG, Ovesen P, et al. Pregnancy outcome and prepregnancy body mass index in 2459 glucose-tolerant Danish women. Am J Obstet Gynecol 2003; 189:239-44..

In investigating the relationship of high maternal pre-pregnancy BMI or gestational weight gain and increased offspring body composition at various ages, the majority of studies have employed double indirect methods (bioelectrical impedance and anthropometric measurements) ⁷7. Laitinen J, Power C, Jarvelin MR. Family social class, maternal body mass index, childhood body mass index, and age at menarche as predictors of adult obesity. Am J Clin Nutr 2001; 74:287-94.,⁸8. Tequeanes AL, Gigante DP, Assuncao MC, Chica DA, Horta BL. Maternal anthropometry is associated with the body mass index and waist:height ratio of offspring at 23 years of age. J Nutr 2009; 139:750-4.,²¹21. Koupil I, Toivanen P. Social and early-life determinants of overweight and obesity in 18-year-old Swedish men. Int J Obes (Lond) 2008; 32:73-81.,²²22. Stuebe AM, Forman MR, Michels KB. Maternal-recalled gestational weight gain, pre-pregnancy body mass index, and obesity in the daughter. Int J Obes (Lond) 2009; 33:743-52. that use a two-component model, dividing body weight into fat mass and fat free mass ²³23. Wells JC, Fuller NJ, Dewit O, Fewtrell MS, Elia M, Cole TJ. Four-component model of body composition in children: density and hydration of fat-free mass and comparison with simpler models. Am J Clin Nutr 1999; 69:904-12.. Recently indirect measuring methods including air displacement plethysmography (ADP), dual energy X-ray absorptiometry (DEXA), total body water (TBW), and body electrical conductivity (TOBEC) have been introduced to the assessment of body composition. These indirect measuring methods are based on a three- or four-compartment model, providing accurate measurements of body fat, lean mass, bone mass, and TBW ²³23. Wells JC, Fuller NJ, Dewit O, Fewtrell MS, Elia M, Cole TJ. Four-component model of body composition in children: density and hydration of fat-free mass and comparison with simpler models. Am J Clin Nutr 1999; 69:904-12.,²⁴24. Wells JC, Fewtrell MS. Measuring body composition. Arch Dis Child 2006; 91:612-7..

This review aimed to: (a) identify studies that investigated the relationship between maternal pre-pregnancy BMI and/or gestational weight gain and offspring fat mass, lean mass, fat-free mass, fat mass index, fat free mass index, lean mass index, body fat percent as measured by indirect methods; and (b) calculate a pooled measure of the strength of the association.

Methods

This systematic review included studies published between the beginning of the indexing by databases until August 2015. The reporting guidance included in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement followed ²⁵25. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6:e1000097..

a) Eligibility criteria: prospective or retrospective cohorts, case-control studies, cross-sectional and randomized controlled trials that evaluated the association between maternal pre-pregnancy BMI and/or gestational weight gain with offspring body composition by indirect methods were eligible for the review. Participants included mother-offspring pairs with the exception of outcomes measured in adolescents and adult populations. Measurements of the outcomes were obtained by DEXA, ADP or TOBEC equipments (indirect methods).

b) Search strategy: a search in the electronic MEDLINE, LILACS and SciELO databases and cited references of the select articles was performed. The search was restricted to publications in English, French, Portuguese, Spanish and Italian and original studies in humans. The Medical Subject Headings (MeSH) descriptors used were: “ maternal weight, over-nutrition, anthropometry, under-nutrition, body mass index, size, obesity, nutritional status ”; OR “ prenatal body mass index, obesity, weight, and height ”; OR “ pre-pregnancy weight, obesity, body mass index ”; OR “ pregnancy weight gain ”; OR “ gestational weight gain ” combined with “ body composition ”, “ body fat ”, “ body fat percentage ”, “ fat mass ”, “ lean mass ”, “ fat mass index ”, “ lean mass index ”, “ fat free mas s”, “ adiposity ”, “ ADP ”, “ TOBEC ” and “ DEXA ”.

c) Data collection process: the study selection was conducted in duplicate by two independent evaluators in order to screen articles which were stored in EndNote (http://www.endnote.com; Thomson Reuters, USA). The screening stages were: (1) reading study titles for potential inclusion; (2) reading the abstracts of study titles with potential inclusion and selected the full-text articles; (3) full-text articles screening; and (4) assessment of selected articles. Disagreements among the evaluators regarding study eligibility following abstract and full-text review were solved by consensus.

The criteria for selecting articles to be fully reviewed included: (1) prospective or retrospective cohort or case-control design; (2) studies with maternal pre-pregnancy BMI and/or gestational weight gain as the main maternal exposures; and (3) studies with at least one of the following outcomes: lean mass, fat mass, fat-free mass, body fat percent, lean mass index (LMI), fat mass index (FMI), and high adiposity in children.

d) Data extraction: for data extraction, the two independent evaluators were responsible for collecting primary data from the selected studies, which were stored in Excel (Microsoft Corp., USA). Information related to study characteristics, such as year, city/country, design, inclusion and exclusion criteria, sample size or number of participants, maternal exposure, age of outcome measurement, indirect method of outcome measurement, and analysis adjustment variables was gathered. Outcome data was extracted independently of the type of the measure of effect presented by the authors (mean, relative risk, odd ratio, etc.). Disagreements among the evaluators regarding data items were solved by consensus.

e) Risk of bias in individual studies: to assess the quality of the randomized control trials the 27-items Downs and Black scale was employed ²⁶26. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998; 52:377-84.. 19 items of the original scale were used to assess the quality of observational studies: type of study, hypothesis/aim, outcomes, exposures, participant selection, loss of follow-up, random variability, statistical method, probability values, source population, study sample, bias, data dredging, lengths of follow-up, precision, confounding and power. According to Downs & Black ²⁶26. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998; 52:377-84., randomized controlled trials could achieve a score ranging from 0 to 27 points, and the observational studies 0 to 20 points. Study quality was determined by the higher score.

f) Summary measures: for meta-analysis the data extracted included the mean (M), standard deviation (SD) or standard error of the mean (SEM), and the sample size (N) for two groups of women: underweight/normal-weight and overweight/obese, for each continuous outcome (body fat percent, fat mass and fat-free mass). The aggregated effect of pre-pregnancy BMI was estimated by calculating the standardized mean differences. The random-effects model for fat-free mass (because heterogeneity between studies was detected) and the fixed-effects model for body fat percent and fat mass, and the corresponding 95% confidence intervals (95%CI) were estimated. The aggregated results for these seven studies are presented in forest plot graphics. Meta-regression and subgroup analysis were conducted to examine the impact of moderator variables on fat-free mass standardized mean difference (SMD). Subgroup analysis was considered and the subsets were study sample, outcome age measurement, study design, indirect method to outcome measurement and confounding control. Stata version 12.0 (StataCorp LP, College Station, USA) was used for data analyses.

g) Risk of bias across studies: statistical heterogeneity among studies was assessed with the Q and I² statistics tests. Publication bias was investigated with Begg’s funnel plot and was further assessed using the Egger’s linear regression test method.

Results

A total of 6,561 articles were initially retrieved: 3,972 duplicate records were removed and 2,589 records screened. Studies on animals, basic sciences, and chronic diseases (n = 2,178) were excluded after a first reading of titles, resulting in 411 abstracts to be analyzed. For 349 abstracts in the review, the exclusion criteria considered were: studies that investigated other distal, intermediate or proximal determinants of offspring’s body composition but not maternal pre-pregnancy BMI or gestational weight gain (n = 72); studies investigating offspring growth patterns using only anthropometric methods (n = 99); studies investigating the feeding patterns of pregnant women, parents and children (n = 75); studies analyzing specific groups of women including mothers with gestational diabetes (n = 62); studies investigating fetal programming (n = 23); validation of body composition by indirect methods (n = 18). Only studies that were clearly irrelevant were excluded at the first stage. The full text of identified articles including those where there were disagreements in the initial title/abstract scanning, were reviewed to ensure that the inclusion criteria were met.

Of the 62 remaining articles, 42 were excluded for the following reasons: studies that investigated maternal exposure after pregnancy (n = 5); outcome evaluated by doubly indirect methods (n = 33); outcome in adulthood (n = 2); maternal height and tricipital skinfold thickness exposures (n = 1); exposure evaluated by indirect methods (n = 1). The cited references of the 20 articles selected were reviewed however no additional publications were found. Figure 1 shows the number of articles retrieved, then excluded at each stage of the review process and the corresponding reasons for their exclusion.

Among the 20 articles that met the inclusion criteria, six included both exposures⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³⁰30. Perng W, Gillman MW, Mantzoros CS, Oken E. A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood. Ann Epidemiol 2014; 24:793-800.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.. The average score of the selected articles was 15.4, with a minimum of 13 and a maximum of 18. Table 1 displays a description of the selected studies: first author’s name; city and country where the study was conducted; study design; number (n) of study participants; eligibility criteria; maternal exposures; offspring’s age when the outcome was assessed; indirect methods used for assessment of body composition of offspring; and confounding variables used in the statistical analyses according to maternal exposures.

Studies that assessed the effect of maternal pre-pregnancy BMI

In 16 of the 20 articles selected, maternal pre-pregnancy BMI was the main exposure investigated. Ten studies were conducted in the United States⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³⁰30. Perng W, Gillman MW, Mantzoros CS, Oken E. A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood. Ann Epidemiol 2014; 24:793-800.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁶36. Andres A, Hull HR, Shankar K, Casey PH, Cleves MA, Badger TM. Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity. Obesity 2015; 23:1252-8.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9., two in the United Kingdom ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33., two in Denmark ³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³⁹39. Tanvig M, Vinter CA, Jorgensen JS, Wehberg S, Ovesen PG, Lamont RF, et al. Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study). PLoS One 2014; 9:89590., one in Australia ²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43., one in Brazil³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17., and one in Portugal ⁴⁰40. Pereira-da-Silva L, Cabo C, Moreira AC, Virella D, Guerra T, Camoes T, et al. The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates. Am J Perinatol 2014; 31:875-82. (Table 1). The number of participants in the cohorts ranged from 78 ³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6. to 3,263³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33.. Although these studies applied different inclusion and exclusion criteria, all consistently excluded premature newborns, those with congenital abnormalities, offspring of mothers with a history of pre-gestational or gestational diabetes, and children with chronic diseases. With the exception of five studies ²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁶36. Andres A, Hull HR, Shankar K, Casey PH, Cleves MA, Badger TM. Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity. Obesity 2015; 23:1252-8., all other studies included only Caucasian participants.

All studies except for three ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³⁰30. Perng W, Gillman MW, Mantzoros CS, Oken E. A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood. Ann Epidemiol 2014; 24:793-800.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9., stratified maternal pre-pregnancy BMI to establish maternal overweight and/or obesity. Eight studies measured body composition in newborns ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.,⁴⁰40. Pereira-da-Silva L, Cabo C, Moreira AC, Virella D, Guerra T, Camoes T, et al. The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates. Am J Perinatol 2014; 31:875-82., whilst all other studies measured body composition in childhood (2-11 years of age). The methods for the assessment of body composition included DEXA in eight studies ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³⁰30. Perng W, Gillman MW, Mantzoros CS, Oken E. A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood. Ann Epidemiol 2014; 24:793-800.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁶36. Andres A, Hull HR, Shankar K, Casey PH, Cleves MA, Badger TM. Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity. Obesity 2015; 23:1252-8.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33.,³⁹39. Tanvig M, Vinter CA, Jorgensen JS, Wehberg S, Ovesen PG, Lamont RF, et al. Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study). PLoS One 2014; 9:89590., ADP in seven⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33.and TOBEC in one ²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3. (Table 2).

• Pre-pregnancy BMI and offspring adiposity

Table 2 summarizes the main results of the 16 studies reviewed. 13 reported fat mass ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³⁰30. Perng W, Gillman MW, Mantzoros CS, Oken E. A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood. Ann Epidemiol 2014; 24:793-800.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33.,³⁹39. Tanvig M, Vinter CA, Jorgensen JS, Wehberg S, Ovesen PG, Lamont RF, et al. Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study). PLoS One 2014; 9:89590.,⁴⁰40. Pereira-da-Silva L, Cabo C, Moreira AC, Virella D, Guerra T, Camoes T, et al. The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates. Am J Perinatol 2014; 31:875-82. and two FMI ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17. as the primary outcome. In nine studies ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33.univariate analyses showed a statistically significant positive association between maternal pre-pregnancy BMI and fat mass in offspring. This association remained significant after adjusting for confounders in six of the studies ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33.. The relationship between maternal pre-pregnancy BMI and body fat mass in children was assessed in 13 studies ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁶36. Andres A, Hull HR, Shankar K, Casey PH, Cleves MA, Badger TM. Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity. Obesity 2015; 23:1252-8.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.,³⁹39. Tanvig M, Vinter CA, Jorgensen JS, Wehberg S, Ovesen PG, Lamont RF, et al. Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study). PLoS One 2014; 9:89590.,⁴⁰40. Pereira-da-Silva L, Cabo C, Moreira AC, Virella D, Guerra T, Camoes T, et al. The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates. Am J Perinatol 2014; 31:875-82.and a positive association was reported only following univariate analyses in six studies⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6..

Eight studies included in the meta-analysis ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁹39. Tanvig M, Vinter CA, Jorgensen JS, Wehberg S, Ovesen PG, Lamont RF, et al. Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study). PLoS One 2014; 9:89590.assessed body fat percent and fat mass in infants in the first months of life to six years of age. The SMD between infants of normal weight women and those of overweight or obese women before pregnancy were relatively small: 0.31 (95%CI: 0.23; 0.39) and 0.38 (95%CI: 0.30; 0.46) for body fat percent and fat mass, respectively (I²= 28% and 18.5%; and p value for test of heterogeneity of 0.21 and 0.29, respectively) (Figure 2).

Begg’s funnel plots and Egger’s publication bias plots were used to assess the potential publication bias for body fat percent and fat mass. No publication bias was detected by Egger’s test (p-value = 0.49 for body fat percent and p-value = 0.60 for fat mass).

• Maternal pre-pregnancy BMI andoffspring lean mass or fat-free mass

The relationship of maternal pre-pregnancy BMI with lean mass ³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33., fat-free mass ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁹39. Tanvig M, Vinter CA, Jorgensen JS, Wehberg S, Ovesen PG, Lamont RF, et al. Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study). PLoS One 2014; 9:89590., fat-free mass percent ³⁶36. Andres A, Hull HR, Shankar K, Casey PH, Cleves MA, Badger TM. Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity. Obesity 2015; 23:1252-8.and LMI²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.was assessed in 11 studies (Table 2). Four studies reported a statistically significant positive association following a univariate analysis²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33. and two studies ³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³⁶36. Andres A, Hull HR, Shankar K, Casey PH, Cleves MA, Badger TM. Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity. Obesity 2015; 23:1252-8. after adjusted analysis. In contrast, Gale et al. ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11. reported a significant positive association between pre-pregnancy BMI and LMI in only male offspring and this was no longer significant following adjusted analysis. Furthermore, Hull et al.⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.reported an inverse association. In the aggregate measure analysis, SMD in fat-free mass between children of normal weight women and those of overweight or obese women was significant: 0.21 (95%CI: 0.02; 0.40), I²= 84.9%, test for heterogeneity p-value = 0.000 (Figure 2). No publication bias was detected by Egger’s test, p-value = 0.12 for fat-free mass.

In relation to SMD in fat-free mass aggregated analyses, heterogeneity was detected in the visual inspection of the forest plot of studies included in the review, a finding that was supported by statistical evidence. Seeking for causes in the studies’ descriptions, although the eligibility criteria in the seven studies were similar, there was heterogeneity due to variation in the study sample (< 100, ≥ 100) and in outcome age measurement (< 1 week and ≥ 1 week). Methodological heterogeneity was detected at study design (prospective cohort and randomized controlled trial), indirect method to outcome measurement (TOBEC, ADP and DEXA) and at confounding control (crude and adjusted analysis). The joint test for all five covariates provided a p-value = 0.63, indicating no evidence for an association of at least one of the covariates with the size of the pre-pregnancy effect on offspring fat-free mass. A high residual heterogeneity was maintained in the subgroup analyses with an exception of outcome age measurement: SMD = 0.12 (95%CI: -0.03; 0.27), I² = 0.00% in studies with < 1 week outcome age measurement and SMD = 0.27 (95%CI: -0.03; 0.57), I² = 91.2% in studies with outcome age measurement ≥ 1 week.

In summary, whilst some studies report a positive association between maternal pre-pregnancy BMI and the body fat of children, the outcomes have been variably assessed in terms of body fat percent, fat mass or FMI. Therefore it is clear that the majority of studies assessed the relationship between pre-pregnancy BMI and the offspring’s body composition in terms of childhood adiposity rather than the fat-free component.

Studies that assessed the effect of gestational weight gain

Ten studies assessed the relationship between gestational weight gain and offspring body composition ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³⁰30. Perng W, Gillman MW, Mantzoros CS, Oken E. A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood. Ann Epidemiol 2014; 24:793-800.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51.,⁴³43. Estampador AC, Pomeroy J, Renstrom F, Nelson SM, Mogren I, Persson M, et al. Infant body composition and adipokine concentrations in relation to maternal gestational weight gain. Diabetes Care 2014; 37:1432-8.,⁴⁴44. Henriksson P, Eriksson B, Forsum E, Lof M. Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition. Pediatr Obes 2015; 10: 388-94. Four studies³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51.,⁴⁴44. Henriksson P, Eriksson B, Forsum E, Lof M. Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition. Pediatr Obes 2015; 10: 388-94.assessed gestational weight gain according to pre-pregnancy BMI and divided it into categories as recommended by the Institute of Medicine of the U.S. National Academy of Sciences ⁴⁵45. Institute of Medicine; National Research Council. Weight gain during pregnancy: reexamining the Guidelines. Washington DC: National Academies Press; 2009.. Sewell et al. ²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3. applied a pre-pregnancy BMI cut-off ≥ 25kg/m². Seven studies assessed gestational weight gain as a continuous variable ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³⁰30. Perng W, Gillman MW, Mantzoros CS, Oken E. A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood. Ann Epidemiol 2014; 24:793-800.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51.. Six studies measured body composition in newborns⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51.,⁴⁴44. Henriksson P, Eriksson B, Forsum E, Lof M. Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition. Pediatr Obes 2015; 10: 388-94., one in children under a year in age ⁴³43. Estampador AC, Pomeroy J, Renstrom F, Nelson SM, Mogren I, Persson M, et al. Infant body composition and adipokine concentrations in relation to maternal gestational weight gain. Diabetes Care 2014; 37:1432-8. and five in children from 3-10 years of age ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³⁰30. Perng W, Gillman MW, Mantzoros CS, Oken E. A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood. Ann Epidemiol 2014; 24:793-800.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51.,⁴³43. Estampador AC, Pomeroy J, Renstrom F, Nelson SM, Mogren I, Persson M, et al. Infant body composition and adipokine concentrations in relation to maternal gestational weight gain. Diabetes Care 2014; 37:1432-8..

• Maternal gestational weight gain and offspring adiposity

The relationship between gestational weight gain and body fat percent was evaluated in seven studies ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴⁴44. Henriksson P, Eriksson B, Forsum E, Lof M. Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition. Pediatr Obes 2015; 10: 388-94., fat mass in nine ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³⁶36. Andres A, Hull HR, Shankar K, Casey PH, Cleves MA, Badger TM. Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity. Obesity 2015; 23:1252-8.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.,³⁹39. Tanvig M, Vinter CA, Jorgensen JS, Wehberg S, Ovesen PG, Lamont RF, et al. Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study). PLoS One 2014; 9:89590.,⁴⁰40. Pereira-da-Silva L, Cabo C, Moreira AC, Virella D, Guerra T, Camoes T, et al. The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates. Am J Perinatol 2014; 31:875-82.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴³43. Estampador AC, Pomeroy J, Renstrom F, Nelson SM, Mogren I, Persson M, et al. Infant body composition and adipokine concentrations in relation to maternal gestational weight gain. Diabetes Care 2014; 37:1432-8., and FMI in two ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17. (Table 3). Five studies reported a statistically significant positive effect of gestational weight gain on body fat percent in univariate analysis ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴⁴44. Henriksson P, Eriksson B, Forsum E, Lof M. Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition. Pediatr Obes 2015; 10: 388-94.and three studies ²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.reported a positive effect between gestational weight gain and body fat percent in the multivariate analysis. In addition, a significant direct association between gestational weight gain and fat mass was found following univariate analysis in four studies ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51..

• Maternal gestational weight gain and offspring lean mass or fat-free mass

The relationship of maternal gestational weight gain and fat-free mass was evaluated in seven studies ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51.,⁴³43. Estampador AC, Pomeroy J, Renstrom F, Nelson SM, Mogren I, Persson M, et al. Infant body composition and adipokine concentrations in relation to maternal gestational weight gain. Diabetes Care 2014; 37:1432-8.,⁴⁴44. Henriksson P, Eriksson B, Forsum E, Lof M. Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition. Pediatr Obes 2015; 10: 388-94. and between maternal gestational weight gain and LMI or FFMI (fat free mass index) in two²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17. (Table 3). A positive effect of gestational weight gain on fat-free mass was reported in six studies ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51.,⁴⁴44. Henriksson P, Eriksson B, Forsum E, Lof M. Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition. Pediatr Obes 2015; 10: 388-94., and this association was statistically significant in three of them ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.. Gale et al. ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11. however reported an inverse association of gestational weight gain on LMI.

The crude analyses of the studies that categorized gestational weight gain according to maternal pre-pregnancy BMI showed that children of overweight or obese mothers, with an adequate or excessive gestational weight gain were more likely to have a high fat mass ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51.,⁴³43. Estampador AC, Pomeroy J, Renstrom F, Nelson SM, Mogren I, Persson M, et al. Infant body composition and adipokine concentrations in relation to maternal gestational weight gain. Diabetes Care 2014; 37:1432-8., body fat percent ⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,⁴¹41. Josefson JL, Hoffmann JA, Metzger BE. Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity. Pediatr Obes 2013; 8:e33-6.,⁴⁴44. Henriksson P, Eriksson B, Forsum E, Lof M. Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition. Pediatr Obes 2015; 10: 388-94., and FFMI²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.compared to newborns of mothers with normal maternal pre-pregnancy BMI with adequate or excessive weight gain (Table 3).

Discussion

This review suggests that children born from mothers with normal maternal pre-pregnancy BMI have lower fat mass and body fat percent than those born from overweight or obese mothers ²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁶36. Andres A, Hull HR, Shankar K, Casey PH, Cleves MA, Badger TM. Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity. Obesity 2015; 23:1252-8.,³⁷37. Starling AP, Brinton JT, Glueck DH, Shapiro AL, Harrod CS, Lynch AM, et al. Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 2015; 101:302-9.,⁴⁰40. Pereira-da-Silva L, Cabo C, Moreira AC, Virella D, Guerra T, Camoes T, et al. The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates. Am J Perinatol 2014; 31:875-82.. The aggregate measure estimated a significantly small difference in mean fat mass and body fat percent in the first months of life between children of overweight or obese mothers and those from mothers with normal maternal pre-pregnancy BMI. The visual inspection of the forest plot showed that effect size and direction of associations described by Hull et al. ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6. and Tanvig et al.³⁹39. Tanvig M, Vinter CA, Jorgensen JS, Wehberg S, Ovesen PG, Lamont RF, et al. Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study). PLoS One 2014; 9:89590. are clearly different. In fact the sample size of the studies can explain such a discrepancy, since both studies have less than 100 participants. There was a significant difference in terms of fat-free mass; random-effects model of meta-analysis shows a significant association of maternal pre-pregnancy BMI and offspring fat mass, body fat percent and fat-free mass. The databases included studies conducted in high and middle income countries, so the meta-analysis lacks information from low income countries populations. An aggregate analysis of gestational weight gain and fat mass, body fat percent or fat-free mass could not be performed.

There are few studies investigating the effect of maternal pre-pregnancy BMI or gestational weight gain on children’s body composition as measured by indirect methods. Consequently, only 20 articles met the inclusion criteria for this review, of which ten assessed the maternal pre-pregnancy BMI, four the gestational weight gain and six both exposures. No studies with negative results were found. Therefore, publication bias can be present ⁴⁶46. Grimes DA, Schulz KF. Bias and causal associations in observational research. Lancet 2002; 359:248-52.. In addition, studies assessing children’s body composition by indirect methods conducted in low-income countries were not found in the literature search.

Several methodological aspects of the studies reviewed require consideration. Firstly, four studies used pre-pregnancy BMI or gestational weight gain information as determined by maternal weight data from medical records. Two studies used maternal weight measurements and four studies relied upon self-reported maternal weight information allowing for recall bias. Indeed, studies that evaluated the accuracy of self-reported maternal weight found that women underestimated their own weight ⁴⁷47. Engstrom JL, Paterson SA, Doherty A, Trabulsi M, Speer KL. Accuracy of self-reported height and weight in women: an integrative review of the literature. J Midwifery Womens Health 2003; 48: 338-45. which may result in a miscalculation of pre-pregnancy BMI or gestational weight gain and biased categorization of pregnant women, indicating exposure bias ⁴⁶46. Grimes DA, Schulz KF. Bias and causal associations in observational research. Lancet 2002; 359:248-52.,⁴⁸48. Greenland S, Robins JM. Confounding and misclassification. Am J Epidemiol 1985; 122:495-506..

Secondly, the recent publication period of the 20 articles (between 2005 and 2015) is probably due to the outcomes definition employed. Previously validated studies of DEXA and ADP are available in the literature from 1980 to 1990, respectively. These are however, costly equipment that require operation by trained personnel and constant maintenance.

Thirdly, a lack of homogeneity in maternal pre-pregnancy BMI categorization in two or more groups using different cutoffs was found in the literature search ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁷27. Au CP, Raynes-Greenow CH, Turner RM, Carberry AE, Jeffery H. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study. Early Hum Dev 2013; 89:839-43.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³³33. Shapiro AL, Schmiege SJ, Brinton JT, Glueck D, Crume TL, Friedman JE, et al. Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 2015; 58:937-41.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁹39. Tanvig M, Vinter CA, Jorgensen JS, Wehberg S, Ovesen PG, Lamont RF, et al. Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study). PLoS One 2014; 9:89590.,⁴⁰40. Pereira-da-Silva L, Cabo C, Moreira AC, Virella D, Guerra T, Camoes T, et al. The adjusted effect of maternal body mass index, energy and macronutrient intakes during pregnancy, and gestational weight gain on body composition of full-term neonates. Am J Perinatol 2014; 31:875-82.. Lack of definition of cutoff points³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33. was also observed. These may have unpredictably underestimated or overestimated the effect of maternal pre-pregnancy BMI and gestational weight gain on offspring body composition.

Fourth, confounding variables showed a wide heterogeneity. Child’s age, gender and breastfeeding were not investigated as potential effect modifiers, and some studies included these variables in the multivariate analysis. A single study included an analysis stratified by gender ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.and two others investigated current children’s weight as an effect modifier²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6..

Fifth, few studies included socioeconomic characteristics as confounding variables in the adjusted analysis. However, the effect of environmental factors was present in the four studies that adjusted for family income, education level, race, and maternal smoking during pregnancy ³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33.strengthening the association (negative confounding) ⁴⁹49. McDonald SD, Han Z, Mulla S, Beyene J; Knowledge Synthesis Group. Overweight and obesity in mothers and risk of preterm birth and low birth weight infants: systematic review and meta-analyses. BMJ 2010; 341:c3428.. The history of maternal smoking during pregnancy was considered in the adjusted analysis of eight studies ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.,³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.,³²32. Carlsen EM, Renault KM, Norgaard K, Nilas L, Jensen JE, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr 2014; 103:939-45.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51.,⁴⁴44. Henriksson P, Eriksson B, Forsum E, Lof M. Gestational weight gain according to Institute of Medicine recommendations in relation to infant size and body composition. Pediatr Obes 2015; 10: 388-94.. The maternal smoking during pregnancy is a well-known cause of growth restriction and low birth-weight and recent studies also suggested that pre-natal smoking compromises infant growth ²2. Kramer MS. Determinants of low birth weight: methodological assessment and meta-analysis. Ann Nutr Metab 1987; 65:663-737.,²¹21. Koupil I, Toivanen P. Social and early-life determinants of overweight and obesity in 18-year-old Swedish men. Int J Obes (Lond) 2008; 32:73-81.,⁴⁹49. McDonald SD, Han Z, Mulla S, Beyene J; Knowledge Synthesis Group. Overweight and obesity in mothers and risk of preterm birth and low birth weight infants: systematic review and meta-analyses. BMJ 2010; 341:c3428.. The mechanism underlying this association is unknown. Some speculate that this association may result from confounding. Mothers who smoke during pregnancy may provide a different social environment for the offspring than mothers who do not smoke ²¹21. Koupil I, Toivanen P. Social and early-life determinants of overweight and obesity in 18-year-old Swedish men. Int J Obes (Lond) 2008; 32:73-81.,⁴²42. Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010; 91:1745-51..

On the other hand, the inclusion of current child characteristics such as height, weight, conditional weight gain or birth weight as confounding variables seems to be inappropriate ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11.,³⁴34. Berkowitz RI, Stallings VA, Maislin G, Stunkard AJ. Growth of children at high risk of obesity during the first 6 y of life: implications for prevention. Am J Clin Nutr 2005; 81:140-6.,³⁵35. Burdette HL, Whitaker RC, Hall WC, Daniels SR. Maternal infant-feeding style and children's adiposity at 5 years of age. Arch Pediatr Adolesc Med 2006; 160:513-20.,³⁶36. Andres A, Hull HR, Shankar K, Casey PH, Cleves MA, Badger TM. Longitudinal body composition of children born to mothers with normal weight, overweight, and obesity. Obesity 2015; 23:1252-8.,³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33.. These variables would more likely have a mediating rather than a confounding effect on the relationship between pre-pregnancy BMI and gestational weight gain with offspring body composition ⁴⁸48. Greenland S, Robins JM. Confounding and misclassification. Am J Epidemiol 1985; 122:495-506.,⁵⁰50. Christenfeld NJ, Sloan RP, Carroll D, Greenland S. Risk factors, confounding, and the illusion of statistical control. Psychosom Med 2004; 66:868-75..

Different studies have reported a positive association between maternal pre-pregnancy BMI and the weight of children born at full term ¹¹11. Ehrenberg HM, Mercer BM, Catalano PM. The influence of obesity and diabetes on the prevalence of macrosomia. Am J Obstet Gynecol 2004; 191:964-8.,¹³13. Surkan PJ, Hsieh CC, Johansson AL, Dickman PW, Cnattingius S. Reasons for increasing trends in large for gestational age births. Obstet Gynecol 2004; 104:720-6.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.. Since the first study on the relationship between children’s body composition and maternal pre-pregnancy BMI or gestational weight gain as the exposure published in 2001 ⁷7. Laitinen J, Power C, Jarvelin MR. Family social class, maternal body mass index, childhood body mass index, and age at menarche as predictors of adult obesity. Am J Clin Nutr 2001; 74:287-94., evidence shows that the incidence of newborns weighing more than 4,000g at birth increases as pre-pregnancy BMI shifts from normal to obesity ⁵¹51. Weiss JL, Malone FD, Emig D, Ball RH, Nyberg DA, Comstock CH, et al. Obesity, obstetric complications and cesarean delivery rate: a population-based screening study. Am J Obstet Gynecol 2004; 190:1091-7.. Due to the availability of indirect methods for body composition the fat mass and fat-free mass arose as new components of birth weight. Studies ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3. have reported that in full-term newborns, fat-free mass accounts for 70-87% of the variation in birth weight. In the relationship of pre-pregnancy BMI with children’s body composition born at full-term to overweight/obese mothers, fat-free mass accounts for 61-75% variation on birth weight while it accounts for 74-89% variation in those who are born from mothers with normal pre-pregnancy BMI ⁵5. Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA. Impact of maternal body mass index on neonate birthweight and body composition. Am J Obstet Gynecol 2008; 198:416.e1-6.,⁶6. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 2011; 205:211.e1-7.,²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3.. Thus, an increase in birth weight that is associated with maternal pre-pregnancy BMI may be primarily attributed to an increase in FM rather than fat-free mass ²⁹29. Sewell MF, Huston-Presley L, Super DM, Catalano P. Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006; 195:1100-3..

Gale et al. ²⁸28. Gale CR, Javaid MK, Robinson SM, Law CM, Godfrey KM, Cooper C. Maternal size in pregnancy and body composition in children. J Clin Endocrinol Metab 2007; 92:3904-11. and Castillo et al.³¹31. Castillo H, Santos IS, Matijasevich A. Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography. Matern Child Nutr 2015; 11:606-17.were the studies that provided data on FMI, FFMI and LMI. Children can have different percentages of fat mass due to different absolute amounts of fat mass but equivalent amounts of fat-free mass or different absolute amounts of fat-free mass and same amounts of fat mass. Because of these relations the normalization of fat mass and lean mass measures for squared height (kg/m²) is recommended to improve the sensitivity to detect changes in body composition measurements ²³23. Wells JC, Fuller NJ, Dewit O, Fewtrell MS, Elia M, Cole TJ. Four-component model of body composition in children: density and hydration of fat-free mass and comparison with simpler models. Am J Clin Nutr 1999; 69:904-12..

Fetal over-nutrition hypothesis is one mechanism that has been suggested to explain the relationship between maternal pre-pregnancy BMI and gestational body composition and offspring body composition. So the relationship between maternal gestational obesity and offspring obesity could be explained by the effect of the exposure to high maternal plasma glucose, free fatty acid and amino acids concentration during pregnancy carrying lifelong changes in fetal appetite, neuroendocrine function or energy metabolism and an increased risk for metabolic and cardiovascular diseases after birth ¹1. Symonds ME, Mendez MA, Meltzer HM, Koletzko B, Godfrey K, Forsyth S, et al. Early life nutritional programming of obesity: mother-child cohort studies. Ann Nutr Metab 2013; 62:137-45.,⁴4. Armitage JA, Poston L, Taylor PD. Developmental origins of obesity and the metabolic syndrome: the role of maternal obesity. Front Horm Res 2008; 36:73-84..

Studies on intergenerational heritability with family members suggest a role of genetic factors in determining individual differences in adiposity ⁵²52. Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 1997; 27:325-51.. Therefore, a variant of the fat mass and obesity associated gene in homozygous individuals appears to increase the risk of obesity, when compared to individuals without the allele. The same is seen for fat mass in children ⁵³53. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316:889-94.. Lawlor et al. ³⁸38. Lawlor DA, Timpson NJ, Harbord RM, Leary S, Ness A, McCarthy MI, et al. Exploring the developmental overnutrition hypothesis using parental-offspring associations and FTO as an instrumental variable. PLoS Med 2008; 5:33. investigated the effect of pre-pregnancy BMI on adiposity in children aged 9-11 years and found that the effect of maternal pre-pregnancy BMI and of the fat mass and obesity associated gene on children FM lost statistical significance after adjusting for child’s fat mass and obesity associated as an instrumental variable. The mechanisms involved in the association of the fat mass and obesity associated gene and the high adiposity are still unclear.

From a perspective of disease prevention and health promotion, maternal obesity is a potentially preventable cause to reduce the disease and mortality burden in childhood. Yet prenatal counseling should be cautious when advising overweight or obese women to optimize their weight before pregnancy. McDonald et al. ⁴⁹49. McDonald SD, Han Z, Mulla S, Beyene J; Knowledge Synthesis Group. Overweight and obesity in mothers and risk of preterm birth and low birth weight infants: systematic review and meta-analyses. BMJ 2010; 341:c3428. argued that maternal overweight/obesity may have a beneficial effect on the survival of children born with low birth weight in low-income countries despite the increased risk of preterm birth in this group.

To our knowledge, this is the first review investigating children’s body composition assessed by indirect methods associated with maternal pre-pregnancy BMI and gestational weight gain and highlights the importance of new studies with appropriate methodology. Given the small number of publications with a number of methodological limitations found in this systematic review and meta-analysis, further investigations are required to evidence causality criteria and to strengthen the association between BMI and gestational weight gain and children’s body composition. Therefore, fetal growth monitoring during pregnancy with the assessment of pre-gestational and gestational maternal body composition (by other more accurate methods than maternal weight) are required as well as the use of maternal and children’s genetic instrumental variables.

Acknowledgments

We would like to thank the following organizations for their support in the production of knowledge for this study: Postgraduate Program in Epidemiology at the Pelotas Federal University and Wellcome Trust.

References

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